Cone-Rod Dystrophies, X-Linked
Patient Information
Characteristics
Background and History
Gene mutations cause a large number of disorders that result in vision loss. These impact the retina lining the back of the eye which is the tissue that responds to light. The retina contains two types of cells called photoreceptors, the cones which enable us to see color, and the rods that respond to dimmer light and enable us to see at night. Some mutations impact primarily cone function and others primarily rod function. The former are known as cone-rod dystrophies, while the latter are often referred to as rod-cone dystrophies. However, while either type of cell dysfunction may be predominant, in most cases progression of disease eventually impacts both resulting in loss of color perception difficulty seeing at night. The cone-rod dystrophies are progressive disorders with symptoms that worsen with age.
Clinical Correlations
Among the cone-rod dystrophies caused by gene changes, there are three that affect primarily males. These are due to mutations on the X chromosome. The first symptoms usually are extreme sensitivity to light beginning in the second and third decades of life followed by some decrease in vision. Loss of some color vision is experienced by most patients at about the same time. Many patients have normal or near normal vision early in their disease but after several decades they often become legally blind. Eventually all color vision is lost and many individuals notice difficulty seeing at night and experience loss of side vision. Early and extreme near-sightedness is often a feature as well.
There are no systemic symptoms in most cases.
Genetics
Inheritance
The X-linked cone-rod dystrophies affect primarily males who have a single X chromosome but some females, who have two X chromosomes, can have some symptoms as well, such as mild vision loss, some light sensitivity, and difficulties with color perception. Thus this group of disorders has patterns of inheritance called X-linked recessive or X-linked dominant (see pedigrees).
Pedigree
X-linked dominant, father affected
X-linked inheritance patterns result when disease-causing mutations are located on the X chromosome. Males have one X chromosome while females have two. A mutation on the male's X chromosome frequently is lethal or renders him unable to reproduce. However, in rare cases when males have children, they can expect that all of then will inherit the condition.
X-linked inheritance patterns result when disease-causing mutations are located on the X chromosome. Males have one X chromosome while females have two. A mutation on the male's X chromosome frequently is lethal or at least renders them unable to reproduce. However, in rare cases when males have children, they can expect that all of then will inherit the condition.
X-linked dominant, mother affected
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
X-linked recessive, father affected
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.
X-linked recessive, carrier mother
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
Diagnosis and Prognosis
The diagnosis of these dystrophies requires a complete eye examination. The symptoms combined with a visual field test, a color vision test, and examination of the retina are usually sufficient to detect the disease. An ERG (electroretinogram) test is done to determine the exact type of disorder.
Early in the disease, correction of the near-sightedness can significantly improve vision. Sensitivity to light requires the use of tinted lenses and those tinted red may even improve vision somewhat. Low vision devices and vocational counseling should be made available.
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